Project Summary The worker response to the World Trade Center (WTC) attacks was unprecedented in scope, involving tens of thousands of traditional (e.g., police) and non-traditional (e.g., construction workers) responders. While posttraumatic stress disorder (PTSD) arising in response to the WTC attacks is prevalent and chronic in 14% of WTC responders, a substantial proportion of this population has remained psychologically resilient to WTC-related PTSD and related symptoms, even more than 15 years after 9/11. Psychological resilience is defined as the ability of an individual to adapt successfully to severe stress, trauma or adversity. The proposed study aims to fill a major gap in our understanding of the neurobiology of psychological resilience by using state-of-the-art functional magnetic resonance imaging (fMRI) methods to characterize between-group functional differences in neural circuits underlying three of the most widely replicated psychological domains ?and potentially modifiable protective factors? associated with resilience: (1) emotion regulation (emotion processing neural circuits), (2) positive emotions (reward processing neural circuits), and (3) the ability to establish and nurture a supportive social network (social cognition neural circuits) in a diverse sample of 105 WTC responders. Characterization of the function of these neural circuits in resilient individuals is critical to understanding the etiology of psychological resilience, as well as to informing resilience-promoting prevention and treatment efforts. WTC responders will be recruited into three groups: highly resilient WTC responders, who have remained psychologically resilient despite enduring severe WTC-related exposures (n=35), and two comparison groups of WTC responders: (1) a symptomatic group with chronic, clinically significant PTSD symptoms (n=35), and (2) a low WTC-exposed control group without psychiatric disorder, who experienced significantly lower levels of WTC-related exposures (n=35). WTC responders will be recruited from a large responder cohort followed prospectively at the WTC Health Program at the Icahn School of Medicine at Mount Sinai, and who have participated in an ongoing study of genomic and neuroendocrine biomarkers of psychological risk and resilience (#3U01OH010407-01S1). The ultimate goal of this study is to develop an integrative, data-driven model to examine how patterns of brain activation across functional domains give rise to distinct mechanisms underlying resilience, and how these neural mechanisms interrelate with behavioral (e.g., emotion regulation, reward responses, social cognition) and psychosocial (e.g., coping self-efficacy, positive emotions, social connectedness) factors implicated in resilience. Results of this study will be used to inform personalized and targeted prevention and treatment approaches that bolster function of specific neural circuits and help promote psychological resilience in WTC and other disaster responders, as well as other populations of trauma survivors.